rs2069952

Positions:

• chr20-35176148-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006404.5(PROCR):​c.323-20C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 1,610,778 control chromosomes in the GnomAD database, including 267,278 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.62 (30044 hom., cov: 31)
  • Exomes 𝑓: 0.57 (237234 hom.)
• Consequence: PROCR NM_006404.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.260

Genes affected

PROCR (HGNC:9452): (protein C receptor) The protein encoded by this gene is a receptor for activated protein C, a serine protease activated by and involved in the blood coagulation pathway. The encoded protein is an N-glycosylated type I membrane protein that enhances the activation of protein C. Mutations in this gene have been associated with venous thromboembolism and myocardial infarction, as well as with late fetal loss during pregnancy. The encoded protein may also play a role in malarial infection and has been associated with cancer. [provided by RefSeq, Jul 2013]

MMP24-AS1-EDEM2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PROCR	NM_006404.5	c.323-20C>T		intron_variant		ENST00000216968.5
MMP24-AS1-EDEM2	NM_001355008.2	c.-101-10277G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PROCR	ENST00000216968.5	c.323-20C>T		intron_variant		1	NM_006404.5	P1
PROCR	ENST00000635377.1	c.223-20C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.615 AC: 93443 AN: 151842 Hom.: 29989 Cov.: 31

Gnomad AFR AF: 0.803

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.599

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.671

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.557

Gnomad OTH AF: 0.580

GnomAD3 exomes AF: 0.555 AC: 138199 AN: 249030 Hom.: 40282 AF XY: 0.564 AC XY: 76024 AN XY: 134864

Gnomad AFR exome AF: 0.811

Gnomad AMR exome AF: 0.359

Gnomad ASJ exome AF: 0.599

Gnomad EAS exome AF: 0.372

Gnomad SAS exome AF: 0.680

Gnomad FIN exome AF: 0.575

Gnomad NFE exome AF: 0.567

Gnomad OTH exome AF: 0.550

GnomAD4 exome AF: 0.565 AC: 824342 AN: 1458818 Hom.: 237234 Cov.: 47 AF XY: 0.568 AC XY: 412507 AN XY: 725928

Gnomad4 AFR exome AF: 0.818

Gnomad4 AMR exome AF: 0.374

Gnomad4 ASJ exome AF: 0.600

Gnomad4 EAS exome AF: 0.322

Gnomad4 SAS exome AF: 0.677

Gnomad4 FIN exome AF: 0.573

Gnomad4 NFE exome AF: 0.563

Gnomad4 OTH exome AF: 0.575

GnomAD4 genome AF: 0.616 AC: 93553 AN: 151960 Hom.: 30044 Cov.: 31 AF XY: 0.615 AC XY: 45653 AN XY: 74266

Gnomad4 AFR AF: 0.803

Gnomad4 AMR AF: 0.485

Gnomad4 ASJ AF: 0.599

Gnomad4 EAS AF: 0.358

Gnomad4 SAS AF: 0.670

Gnomad4 FIN AF: 0.569

Gnomad4 NFE AF: 0.557

Gnomad4 OTH AF: 0.585

Alfa AF: 0.573 Hom.: 6352

Bravo AF: 0.609

Asia WGS AF: 0.579 AC: 2016 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	14
DANN	Benign	0.87

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2069952; hg19: chr20-33763951; COSMIC: COSV53826106; COSMIC: COSV53826106;